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Human metabolic response to systemic inflammation: assessment of the concordance between experimental endotoxemia and clinical cases of sepsis/SIRS
- 作者:Kubra Kamisoglu (1)
Beatrice Haimovich (2) Steve E Calvano (2) Susette M Coyle (2) Siobhan A Corbett (2) Raymond J Langley (3) Stephen F Kingsmore (4) (5) Ioannis P Androulakis (1) (2) (6)
1. Department of Chemical and Biochemical Engineering ; Rutgers University ; Piscataway ; NJ ; 08854 ; USA 2. Department of Surgery ; Rutgers - Robert Wood Johnson Medical School ; New Brunswick ; NJ ; 08901 ; USA 3. Department of Respiratory Immunology ; Lovelace Respiratory Research Institute ; Albuquerque ; NM ; 87108 ; USA 4. Center for Pediatric Genomic Medicine ; Children鈥檚 Mercy ; Kansas City ; MO ; 64108 ; USA 5. Departments of Pediatrics and Obstetrics/Gynecology ; University of Missouri ; Kansas City ; MO ; 64108 ; USA 6. Department of Biomedical Engineering ; Rutgers University ; 599 Taylor Road ; Piscataway ; NJ ; 08854 ; USA
- 刊名:Critical Care
- 出版年:2015
- 出版时间:December 2015
- 年:2015
- 卷:19
- 期:1
- 全文大小:621 KB
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- 刊物主题:Intensive / Critical Care Medicine; Emergency Medicine;
- 出版者:BioMed Central
- ISSN:1364-8535
文摘
Introduction Two recent, independent, studies conducted novel metabolomics analyses relevant to human sepsis progression; one was a human model of endotoxin (lipopolysaccharide (LPS)) challenge (experimental endotoxemia) and the other was community acquired pneumonia and sepsis outcome diagnostic study (CAPSOD). The purpose of the present study was to assess the concordance of metabolic responses to LPS and community-acquired sepsis. Methods We tested the hypothesis that the patterns of metabolic response elicited by endotoxin would agree with those in clinical sepsis. Alterations in the plasma metabolome of the subjects challenged with LPS were compared with those of sepsis patients who had been stratified into two groups: sepsis patients with confirmed infection and non-infected patients who exhibited systemic inflammatory response syndrome (SIRS) criteria. Common metabolites between endotoxemia and both these groups were individually identified, together with their direction of change and functional classifications. Results Response to endotoxemia at the metabolome level elicited characteristics that agree well with those observed in sepsis patients despite the high degree of variability in the response of these patients. Moreover, some distinct features of SIRS have been identified. Upon stratification of sepsis patients based on 28-day survival, the direction of change in 21 of 23 metabolites was the same in endotoxemia and sepsis survival groups. Conclusions The observed concordance in plasma metabolomes of LPS-treated subjects and sepsis survivors strengthens the relevance of endotoxemia to clinical research as a physiological model of community-acquired sepsis, and gives valuable insights into the metabolic changes that constitute a homeostatic response. Furthermore, recapitulation of metabolic differences between sepsis non-survivors and survivors in LPS-treated subjects can enable further research on the development and assessment of rational clinical therapies to prevent sepsis mortality. Compared with earlier studies which focused exclusively on comparing transcriptional dynamics, the distinct metabolomic responses to systemic inflammation with or without confirmed infection, suggest that the metabolome is much better at differentiating these pathophysiologies. Finally, the metabolic changes in the recovering patients shift towards the LPS-induced response pattern strengthening the notion that the metabolic, as well as transcriptional responses, characteristic to the endotoxemia model represent necessary and 鈥渉ealthy鈥?responses to infectious stimuli.
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